Abstract
This case study for the flipped classroom introduces the discovery process used to elucidate how cells make ATP. Data from three seminal primary literature papers and novel (for their time) methods are used to illustrate how scientists determined the mechanism of ATP synthesis via chemiosmosis across a membrane. The story begins with the classic reductionist approach used by many brilliant scientists to figure out familiar pathways such as glycolysis and the Krebs cycle. This method worked so well that there was little reason to think that the elusive intermediates in the ATP pathway wouldn't also be similarly revealed. Mitchell (1961) hinted that this classic approach might not work for ATP synthesis; Jagendorf and Uribe (1966) showed that pH changes (a proton motive force) across a membrane can generate ATP, describing the process of chemiosmosis; Racker and Stoeckenius (1974) described the individual components necessary for ATP synthesis in an artificial system. By taking an historical approach, students learn a basic biochemical concept while also learning that discoveries sometimes take time to be accepted by other scientists.